Bioavailability, which is an index showing the extent to which an administrated drug reaches and acts in the blood in the general circulation, is a clinically significant parameter closely relating to drug efficacy or toxicity. Prediction or control of drug efficacy or toxicity of drugs with low bioavailability is difficult because they sometimes fail to attain the expected drug efficacy or have large intra- or inter-individual variation. Thus, obtaining appropriate bioavailability is important in the development of pharmaceutical products. Orally administered drugs are affected by the gastrointestinal absorption efficiency and metabolism in the liver and gastrointestinal tract. In particular, for poorly soluble drugs, improving drug dissolution from a pharmaceutical preparation or improving drug solubility in water is important to obtain appropriate bioavailability.
4-((1-methylpyrrol-2-yl)-carbonyl)-N-(4-(4-morpholin-1-yl-carbonylpiperidin-1-yl)-phenyl)-1-piperazinecarboxamide or a salt thereof is a drug for preventing and/or treating allergy diseases, inflammatory diseases, degenerative muscle diseases and the like, caused by an inhibitory effect of prostaglandin D synthase, particularly, hematopoietic prostaglandin D synthase (Patent Literature 1). However, there has been a problem of ensuring appropriate bioavailability because of the drug's low absorption and dissolution in the neutral pH range.
To improve drug dissolution and absorption, a method of adding an organic acid is widely known. Reported techniques include, for example, a technique of combining a benzimidazole compound and a pH modifier such as monosodium fumarate (Patent Literature 2), a technique of combining a morphinan derivative and an organic acid such as fumaric acid (Patent Literature 3), and the like.
However, regarding 4-((1-methylpyrrol-2-yl)-carbonyl)-N-(4-(4-morpholin-1-yl-carbonylpiperidin-1-yl)-phenyl)-1-piperazinecarboxamide, there has been no document reporting that dissolution and/or absorption is improved by adding a specific organic acid as an acid additive, as in the present invention.